This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The teams of Caparon and Hultgren at Washington University in St. Louis recently identified the protein toxin (SPN, ~36 kDa) secreted by Streptococcus pyogenes, a Gram-positive bacteria responsible for causing strep throat and flesh eating disease. A novel endogenous inhibitor, named Immunity Factor for SPN (IFS, ~ 22kDa) was recently discovered on the same codon as SPN. IFS forms a stable complex with SPN at a 1:1 molar ratio and inhibits SPN's activity by acting as a competitive inhibitor. The crystal structure of IFS was determined in the Ellenberger group at Washington University in St. Louis (unpublished data). Our goal is to use the high resolution PLIMSTEX protocol to locate the binding interface of IFS to SPN. The crystal structure of the complex is underway.